Proteomic Analysis of m.8296A & #x3e;G Variation in the Mitochondrial < b > < i > tRNA < /i > < /b > < sup > Lys < /sup > Gene

In this study, we aimed to analyze the mitochondrial proteome in a patient with m.8296A#x3e;G variation to elucidate the effects of this mutation at the protein level. Whole-exome sequencing and mitochondrial genome analysis were performed in a patient with sensorineural hearing impairment, cognitive impairment, leukodystrophy, migraine-like headaches, and gastrointestinal dysmotility. Mitochondrial genome analysis identified a homoplasmic m.8296A#x3e;G variation in the mitochondrialtRNALys gene in the proband and unaffected mother. Global mitochondrial proteome analysis was carried out in the muscle mitochondria of the index patient and a control subject. Comparative muscle mitochondrial proteome analysis revealed a total of 13 nuclear-encoded mitochondrial proteins differently expressed with respect to the control. Ten of the 13 proteins were downregulated. Most of the proteins were involved in ATP synthesis and Krebs cycle and have strong interactions with each other. We considered the m.8296A#x3e;G variation to be pathogenic with variable penetrance for our patient ’s phenotype, and this variation led to different expressions of nuclear-encoded proteins involved in energy metabolism.Mol Syndromol
Source: Molecular Syndromology - Category: Molecular Biology Source Type: research